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The COVID-19 global pandemic has broad implications for obstetrical care and perinatal outcomes. As we approach the 2-year mark into an unprecedented international pandemic, this review presents the progress and opportunities for research related to COVID-19 and pregnancy. Research is the basis for evidence-based clinical guidelines, and we aim to provide the structure and guidance for framing COVID-19-related obstetrical research. This structure will pertain not only to this pandemic but future ones as well.

Asymptomatic cervical changes, such as cervical length shortening and dilation, which often occur before spontaneous preterm birth, have been described well in singleton pregnancies with or without history of preterm birth. The current screening strategies available to identify patients at increased risk of spontaneous preterm birth include use of transvaginal ultrasound for cervical length assessment and for detection of a short cervical length (≤25 mm) before 24 weeks of gestation. Whether an additional evaluation of the cervix (ie, via speculum or manual exam) is indicated is often pondered by clinicians and may depend on how short the cervical length is and if there is a history of preterm birth. Based on expert opinion, we developed a novel staging system of asymptomatic cervical changes including the following: cervical length measurement, cervical and membrane appearance on speculum exam, and cervical dilation by manual exam. This staging system, if proven accurate, may aid in standardizing definitions for purposes of patient prognosis, evaluation of intervention efficacy, and clinical management.

Objective The objective of this study was to survey national utilization of cervical length (CL) ultrasound on labor and delivery (L&D) for the evaluation of preterm labor (PTL) and identify provider attitudes and barriers to utilization. Study Design Survey was emailed to Obstetrics and Gynecology Residency and Maternal-Fetal Medicine Fellowship program and advertised via links on obstetric-related Facebook interest groups. The survey was open from August 4, 2020 to January 4, 2021. Characteristics between respondents who did and did not report the use of CL ultrasound for PTL evaluation were compared with chi-square analysis. Results There were 214 respondents across 42 states. One hundred and thirty-four respondents (63%) reported any use of CL in the evaluation of PTL and eighty (37%) denied it. There was a significant difference in practice location, practice type, delivery volume, and region between those who did and did not utilize CL ultrasound on L&D. Those who did use CL ultrasound were more likely to report no barriers to use (40 vs. 4%, p Conclusion CL ultrasound is used nationally in PTL evaluation. However, significant barriers limit widespread adoption. These barriers can be addressed through the dissemination of information and practice guidelines, addition of CL ultrasound education in residency training and through CME opportunities after training, and providing support/resources/access for those looking to add this tool to their practice environment. Key Points

Platelet protease activated receptor-4 (PAR4) Thr120 is a common genetic variant associated with increased platelet activity. Increased platelet activity is implicated in the pathogenesis of preeclampsia and preterm birth.Compare the rate of preeclampsia and preterm birth in pregnant individuals homozygous for PAR4 Thr120 variant vs not.This is a prospective cohort study of patients who delivered November 2020-July 2021. Maternal blood collected on admission for PAR4 genotyping. The primary outcome was the rate of preeclampsia/gestational hypertension in those with Thr/Thr genotype compared with Ala/Thr or Ala/Ala. Secondary outcomes included rates of preterm birth and placental pathology.Three hundred and twenty singletons were included and 52 (16.3%) were PAR4 Thr/Thr. Those PAR4 Thr/Thr were more likely to be Black (67.3% vs 29.5%, p lt; .001), younger (28 ± 6 vs 31 ± 6, p = .004), and have higher body mass index (35.2 ± 6.8 vs 33.1 ± 7.4, p = .047). There was no difference in preeclampsia/gestational hypertension (19.2% vs 22.8%, p = .705). Those Thr/Thr had a significantly higher rate of preterm birth (15.4% vs 3.7%, adjusted odds ratio [aOR] 4.04 [1.47-11.10], p = .007), indicated preterm birth because of fetal growth restriction or preeclampsia (5.8% vs 0.4%, aOR 10.03 [1.48-67.87], p = .02), spontaneous preterm birth (7.7% vs 2.2%, aOR 4.81 [1.27-18.27], p = .02), and placental intervillous thrombosis (18.5% vs 7.9%, aOR 4.12 [1.14-14.92], p = .03).Platelet receptor PAR4 Thr120 is a common variant associated with an increased risk of placental vascular pathology and preterm birth in homozygous individuals. Although a cohort study cannot establish causation, this strong association warrants further exploration.

Randomized trials have found benefits of both vaginal progesterone and 17-alpha-hydroxyprogesterone caproate in the prevention of recurrent preterm birth. A previous meta-analysis directly comparing the two was limited by low-quality evidence, and national and international society guidelines remain conflicting regarding progestin formulation recommended for prevention of recurrent preterm birth. The aim of this updated systematic review with meta-analysis was to evaluate the efficacy of vaginal progesterone compared with 17-alpha-hydroxyprogesterone caproate in the prevention of spontaneous preterm birth in patients with singleton gestations and previous spontaneous preterm birth.Searches were performed in MEDLINE, Ovid, Scopus, ClinicalTrials.gov, the International Prospective Register of Systematic Reviews (PROSPERO), SciELO, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) with the use of a combination of keywords and text words related to "preterm birth," "preterm delivery," "singleton," "cervical length," "progesterone," "progestogens," "vaginal," "17-alpha-hydroxy-progesterone caproate," and "intramuscular" from inception of each database to September 2021. No restrictions for language or geographic location were applied.We included all randomized controlled trials of asymptomatic singleton gestations with previous spontaneous preterm birth that were randomized to prophylactic treatment with either vaginal progesterone (ie, intervention group) or intramuscular 17-alpha-hydroxyprogesterone caproate (ie, comparison group). Post hoc sensitivity analysis was performed for studies with low risk of bias and studies with protocol registration.The primary outcome was preterm birth34 weeks' gestation. The summary measures were reported as relative risks with 95% confidence intervals.Seven randomized controlled trials including 1910 patients were included in the meta-analysis. Patients who received vaginal progesterone had a significantly lower rate of preterm birth at34 weeks (14.7% vs 19.9%; relative risk, 0.74; 95% confidence interval, 0.57-0.96), preterm birth at37 weeks (36.0% vs 46.6%; relative risk, 0.76; 95% confidence interval, 0.69-0.85), and preterm birth at32 weeks of gestation (7.9% vs 13.6%; relative risk, 0.58; 95% confidence interval, 0.39-0.86), compared with women who received intramuscular 17-alpha-hydroxyprogesterone caproate. There were no significant differences in the rate of preterm birth at28 weeks' gestation. Adverse drug reactions were significantly lower in the vaginal progesterone group than in the 17-alpha-hydroxyprogesterone caproate group (15.6% vs 22.2%; relative risk, 0.71; 95% confidence interval, 0.54-0.92). Perinatal mortality was lower in the vaginal progesterone group than in the 17-alpha-hydroxyprogesterone caproate group (2.2% vs 4.4%; relative risk, 0.51; 95% confidence interval, 0.25-1.01). In sensitivity analysis including trials rated with at least 4 Cochrane tools as of "low risk of bias," 4 trials were included (N=575), and there was no longer a significant difference in preterm birth at34 weeks' gestation between vaginal progesterone and 17-alpha-hydroxyprogesterone caproate (12.2% vs 13.9%; relative risk, 0.87; 95% confidence interval, 0.57-1.32).Overall, vaginal progesterone was superior to 17-alpha-hydroxyprogesterone caproate in the prevention of preterm birth at34 weeks' gestation in singleton pregnancies with previous spontaneous preterm birth. Although sensitivity analysis of high-fidelity studies showed the same trend, findings were no longer statistically significant.

BackgroundThe COVID-19 pandemic continues worldwide with fluctuating case numbers in the United States. This pandemic has affected every segment of the population with more recent hospitalizations in the pediatric population. Vertical transmission of COVID-19 is uncommon, but reports show that there are thrombotic, vascular, and inflammatory changes in the placenta to which neonates are prenatally exposed. Individuals exposed in utero to influenza during the 1918 pandemic had increased risk for heart disease, kidney disease, diabetes, stomach disease and hypertension. Early exposure of COVID-19 during fetal life may lead to altered gene expression with potential long-term consequences.ObjectiveTo determine if gene expression is altered in cord blood cells from term neonates who were exposed to COVID-19 during pregnancy and to identify potential gene pathways impacted by maternal COVID-19.MethodsCord blood was collected from 16 term neonates (8 exposed to COVID-19 during pregnancy and 8 controls without exposure to COVID-19). Genome-wide gene expression screening was performed using Human Clariom S gene chips on total RNA extracted from cord blood cells.ResultsWe identified 510 differentially expressed genes (374 genes up-regulated, 136 genes down-regulated, fold change ≥1.5, p-value ≤ 0.05) in cord blood cells associated with exposure to COVID-19 during pregnancy. Ingenuity Pathway Analysis identified important canonical pathways associated with diseases such as cardiovascular disease, hematological disease, embryonic cancer and cellular development. Tox functions related to cardiotoxicity, hepatotoxicity and nephrotoxicity were also altered after exposure to COVID-19 during pregnancy.ConclusionsExposure to COVID-19 during pregnancy induces differential gene expression in cord blood cells. The differentially expressed genes may potentially contribute to cardiac, hepatic, renal and immunological disorders in offspring exposed to COVID-19 during pregnancy. These findings lead to a further understanding of the effects of COVID-19 exposure at an early stage of life and its potential long-term consequences as well as therapeutic targets.

ObjectiveTo describe the profile and specificity of maternal and neonatal cord-blood antibody profile in response SARS-CoV-2 virus exposureMethodsThis is a Prospective cohort study of delivering patients at Thomas Jefferson University Hospital from April 2020-February 2021. Primary objective was to describe unique maternal and fetal antibody epitope titers and specificity in those patients with COVID-19 history. Serologic profile assessed with a multiplex platform. Antigens used were: HA-trimer Influenza A (Hong Kong H3), spike trimers for SARS-CoV-2, SARS-CoV-1, MERS-CoV, and betacoronaviruses HKU-1 and OC43, as well as the spike N-terminal domain (NTD), spike receptor binding domain (RBD), and nucleocapsid protein (N; full length) for SARS-CoV-2.Results112 maternal samples and 101 maternal and cord blood pairs were analyzed. Thirty-seven had a known history of COVID-19 (positive PCR test) in the pregnancy and of those, 17 (47%) were diagnosed with COVID-19 within 30 days of delivery. Fifteen of remaining seventy-six (20%) without a known diagnosis had positive maternal serology. For those with history of COVID-19 we identified robust IgG response in maternal blood to CoV2 nucleocapsid (N), spike (S) full-length and S (RBD) antigens with more modest responses to the S (NTD) antigen. By contrast, the maternal blood IgM response appeared more specific to S (full-length), than N, S (RBD) or S (NTD) epitopes. There were significantly higher maternal and cord blood IgG response not just to CoV2 spike (p < 10−18), but also CoV1 spike (p < 10−9) and MERS spike (p < 10−8). By contrast, maternal IgM responses were more specific to CoV2 (p < 10−19), but to a lesser degree for CoV1 (p < 10−5), and no significant differences for MERS. Maternal and cord-blood IgG were highly correlated for both S and N (R2 = 0.96 and 0.94).ConclusionsPlacental transfer is efficient, with robust N and S responses. Both nucleocapsid and spike antibody responses should be studied for a better understanding of COVID-19 immunity. IgG antibodies are cross reactive with related CoV-1 and MERS spike epitopes while IgM, which cannot cross placenta to provide neonatal passive immunity, is more SARS CoV-2 specific. Neonatal cord blood may have significantly different fine-specificity than maternal blood, despite the high efficiency of IgG transfer.

Objectives The primary objective was to estimate the initiation and adherence rates of 17 α-hydroxyprogesterone caproate (17OHPC) among eligible mothers in a statewide population-based cohort of Medicaid enrollees. The secondary objectives were to (1) determine the association of maternal sociodemographic and clinical characteristics with 17OHPC utilization and (2) assess the real-world effectiveness of 17OHPC on recurrent preterm birth prevention and admission to neonatal intensive care unit (NICU). Study Design This is a retrospective cohort study using a linked, longitudinal administrative dataset of birth certificates and medical assistance claims. Medicaid-enrolled mothers in Pennsylvania were included in this study if they had at least one singleton live birth from 2014 to 2016 following at least one spontaneous preterm birth. Maternal Medicaid claims were used to ascertain the use of 17OHPC from various manufacturers, including compounded formulations. Propensity score matching was used to create a covariate balance between 17OHPC treatment and comparison groups. Results We identified 4,781 Medicaid-covered 17OHPC-eligible pregnancies from 2014 to 2016 in Pennsylvania, 3.4% of all Medicaid-covered singleton live births. The population-based initiation rate was 28.5% among eligible pregnancies. Among initiators, 50% received ≥16 doses as recommended, while 10% received a single dose only. The severity of previous spontaneous preterm birth was the strongest predictor for the initiation and adherence of 17OHPC. In the matched treatment (n = 1,210) and comparison groups (n = 1,210), we found no evidence of 17OHPC effectiveness. The risks of recurrent preterm birth (relative risk [RR] 1.10, 95% confidence interval [CI] 0.97–1.24) and births admitted to NICU (RR 1.00, 95% CI 0.84–1.18) were similar in treated and comparison mothers. Conclusion The 17OHPC-eligible population represented 3.4% of singleton live births. Less than one-third of eligible mothers initiated treatment. Among initiators, 50% were treatment adherent. We found no difference in the risk of recurrent preterm birth or admission to NICU between treatment and comparison groups. Key Points

Objective The aim of the study is to assess the correlation between maternal methadone dose and severity of neonatal abstinence syndrome (NAS) in infants that required pharmacological treatment for NAS. Study Design This is a retrospective analysis of 574 infants ≥35 weeks' gestation exposed to methadone in utero, born between August 2006 and May 2018, and who required pharmacological therapy for NAS. Indicators of NAS severity (duration of morphine treatment, maximum morphine dose, use of phenobarbital, and length of hospitalization) were compared between infants exposed to high (≥200 mg), intermediate (100–199 mg), and low doses ( Results Median (interquartile range) duration of medical treatment with morphine was higher in infants exposed to higher doses of methadone (low dose 23 [14–37] days, intermediate dose 31 [18–45] days, and high dose 35 [20–48] days, p Conclusion Infants exposed to higher methadone doses displayed more severe NAS, as indicated by longer durations of treatment, higher maximum morphine dose, longer duration of hospitalization, and increased likelihood of phenobarbital use. Key Points

Objective This study aimed to evaluate the utilization of aspirin for preeclampsia prevention before and after implementation of a screening tool during nuchal translucency (NT) ultrasound. Study Design One-year prospective cohort study of patients at high risk for preeclampsia after the implementation of a screening tool (postscreen) administered to all patients at check in for NT (11–13 weeks) ultrasound. Prospective cohort was compared with one-year retrospective cohort (prescreen) the year prior (2017). All patients who presented for NT ultrasound in both cohorts were evaluated for the presence of one or more risk factor for preeclampsia with screening tool collected prospectively and chart review retrospectively. Provider recommendation for aspirin determined by documentation in prenatal record. Primary outcome was rate of provider recommendation for aspirin pre versus post screening tool, compared by Chi-square test and adjusted for potential confounders with multiple regression analysis. Results Pre- (n = 156) and postscreen (n = 136) cohorts were similar except for race and multifetal gestation. Prescreen, rate of provider recommendation for aspirin was 74%. Of those with prior preeclampsia, 96% were recommended aspirin, compared with 64% of patients with other risk factors (p Conclusion Prior to implementation of a simple screening questionnaire, approximately 25% of high risk patients did not receive the recommendation of aspirin for preeclampsia prevention. High-risk patients who lack a history of preeclampsia were less likely to be advised of aspirin prophylaxis. Use of a simple universal screening tool at time of NT ultrasound significantly improved utilization of aspirin for preeclampsia prevention and may improve patient outcomes. Key Points

In women with a previous preterm birth, a protocol for serial cervical length screening has been studied and recommended for the identification and treatment of a short cervix. Cervical length screening along with vaginal progesterone has been suggested for low-risk women with singleton pregnancies to treat a short cervix and reduce preterm birth. However, specific protocols for single vs serial ultrasound measuring cervical length in this population are not established. Cost-effectiveness of universal cervical length screening depends on the cost of screening; follow-up of borderline measurements can contribute to increased costs with uncertain benefit.This study aimed to determine the utility of follow-up cervical length screening in otherwise low-risk women with singleton pregnancies with a midtrimester cervical length measurement of 26 to 29 mm through the assessment of the rate of short cervix (≤25 mm) on follow-up ultrasound and subsequent delivery outcomes.This was a 2-year retrospective cohort study at a single urban institution of women with singleton pregnancies with no previous spontaneous preterm birth and an initial transvaginal ultrasound cervical length measurement of 26 to 29 mm identified during universal cervical length screening at time of anatomy ultrasound (18 0/7 to 22 6/7 weeks' gestation). The primary outcome was the rate of short cervix (defined as ≤25 mm on transvaginal ultrasound) on follow-up ultrasound at24 weeks' gestation. Secondary outcomes included the rate of spontaneous preterm birth (37 and34 weeks' gestation).During the study period, there were 2801 women with singleton pregnancies at 18 0/7 to 22 6/7 weeks' gestation with transvaginal ultrasound cervical length screening at time of anatomy scan. Among those women, 201 had a cervical length of 26 of 29 mm, and 184 (7%) had no previous spontaneous preterm birth and were included in the study. Furthermore, 144 women (78%) had a follow-up cervical length completed before 24 weeks' gestation. The mean follow-up interval was 1.5±0.6 weeks. Overall, the percentage of short cervix (≤25 mm) on follow-up was 15% (n=21). Baseline characteristics were similar, but the initial cervical length measurement was shorter in women who subsequently developed a short cervix (26.7±0.8 vs 27.8±1.0; P.01). Delivery outcomes were available for 126 patients. The rate of spontaneous preterm birth at37 weeks' gestation in women with an initial cervical length 26 to 29 mm and subsequent short cervix was significantly higher than the rate of spontaneous preterm birth in a historical cohort of low risk women with an initial cervical length25 mm (16% vs 3%; P=.03). The rate of spontaneous preterm birth at34 weeks' gestation in women with a subsequent short cervix was 11% (2 of 19).Here, approximately 15% of low-risk women with singleton pregnancies with a midtrimester cervical length measurement of 26 to 29 mm will experience cervical shortening of ≤25 mm before 24 weeks' gestation. Compared to women with singleton pregnancies without a history of preterm birth, the rate of spontaneous preterm birth (16%) in women with an initial cervical length of 26 to 29 mm and a subsequent cervical shortening of ≤25 mm is significantly higher. A total of 111 follow-up ultrasounds measuring cervical length would be required to prevent 1 early preterm birth at34 weeks' gestation.

INTRODUCTION: Second trimester asymptomatic cervical dilation is significant risk factor for early preterm birth. The objective of this study is to evaluate whether transvaginal ultrasound cervical length (CL) predicts asymptomatic cervical dilation on physical exam in women with short cervix (CL≤25mm) and no prior preterm birth. MATERIAL AND METHODS: Secondary analysis of a randomized trial on pessary in asymptomatic singletons without prior preterm birth diagnosed with CL≤25mm between 18 0/7– 23 6/7 weeks. Participants had transvaginal ultrasound and physical cervical exam and were randomized to pessary or no pessary with all patients with cervical length≤20mm offered vaginal progesterone. The primary outcome was to determine whether CL was predictive of asymptomatic physical cervical dilation ≥1cm using receiver operating characteristic curve. RESULTS: One-hundred-nineteen women were included. Based on receiver operating characteristic curve, CL ≤11mm was best predictive of cervical dilation ≥1cm, with 75% sensitivity, 80% specificity, and area under the curve 0.73(0.55–0.91), p=0.009. Cervical length ≤11mm had increased incidence of cervical dilation ≥1cm on physical exam (30% vs 3%, odds ratio 12.29 (3.05 to 49.37) p11mm. CONCLUSIONS: Among singletons without prior preterm birth diagnosed with short cervix (≤25mm), CL ≤11mm may identify a subgroup of patients at high risk for asymptomatic cervical dilation and poor perinatal outcome. Physical exam should be considered and adjunctive preterm birth prevention measures should be studied in singletons with CL≤11mm.

To determine the prevalence of low mean corpuscular volume (MCV) in newborn infants admitted to the neonatal intensive care unit and to assess low MCV as a diagnostic test for alpha thalassemia.Retrospective analysis of all infants admitted to the neonatal intensive care unit between January 2010 and October 2018 for which a complete blood count was performed during the first 3 postnatal days. Infants with a low MCV were compared with those with a normal MCV. Infants with positive hemoglobin Bart (Hb Bart) were compared with those withnegative Hb Bart. Low MCV was also evaluated as a diagnostic test for alpha thalassemia.A total of 3851 infants (1386 preterm, 2465 term) met the inclusion criteria and 853 (22.2%) had a low MCV. A low MCV was more common in term (25%) compared with preterm infants (17.1%, P .001). Hb Bart positive newborn screening was identified in 133 infants (3.5%). Hb Bart was positive in 11.1% of infants with low MCV compared with 1.3% with normal MCV (P .001). The sensitivity, specificity, positive predictive value, and negative predictive value of low MCV for the diagnosis of alpha thalassemia were 71.4%, 79.6%, 11.3%, and 98.7%, respectively.As Hb Bart positive newborn screens were seen in only 11.1% of infants with microcytosis, further diagnostic investigation may be warranted in individual infants. Further research to correlate microcytosis with iron status in infants and mothers is needed as well as studies using DNA analysis for the evaluation of alpha thalassemia variants.

Objective This study aimed to identify the incidence of and risk factors for early preterm birth (PTB) (delivery Study Design Retrospective cohort study of singletons without prior PTB diagnosed with short cervix (≤20 mm) between 180/7 and 236/7 weeks. Women who accepted vaginal progesterone and had delivery outcomes available were included. Demographic/obstetric history, cervical length, and pregnancy characteristics compared between women with early PTB versus delivery ≥34 weeks. Multiple logistic regression analysis used to identify predictors; odds ratio for significant factors used to generate a risk score. Risk score and risk of early PTB assessed with receiver operating characteristic curve (ROCC). Perinatal outcomes compared by risk score. Results Among 109 patients included, 29 (27%) had a spontaneous PTB Conclusion A total of 27% of patients with short cervix prescribed vaginal progesterone will have a sPTB

Preterm birth is the leading cause of neonatal morbidity and mortality, and previous preterm birth is one of the strongest risk factors for preterm birth. National and international obstetrical societies have different recommendations regarding progesterone formulation for the prevention of recurrent preterm birth.This study aimed to determine whether vaginal progesterone is superior to 17-hydroxyprogesterone caproate in the prevention of recurrent preterm birth in patients with singleton pregnancies who had a previous spontaneous preterm birth.This was an open-label multicenter pragmatic randomized controlled trial at 5 US centers of patients with singleton pregnancies at24 weeks of gestation who had a previous spontaneous preterm birth randomized 1:1 to either 200 mg vaginal progesterone suppository nightly or 250 mg intramuscular 17-hydroxyprogesterone caproate weekly from 16 to 36 weeks of gestation. Based on the estimated recurrent preterm birth rate of 36% with 17-hydroxyprogesterone caproate, 95 participants were needed in each arm to detect a 50% reduction in preterm birth rate with vaginal progesterone, with 80% power and 2-sided alpha of 0.05. The primary outcome was preterm birth at37 weeks of gestation. Prespecified secondary outcomes included preterm birth at34 and28 weeks of gestation, mean gestational age at delivery, neonatal morbidity and mortality, and measures of adherence. Analysis was by intention to treat. The chi-square test and Student t test were used as appropriate. P.05 was considered significant.Overall, 205 participants were randomized; 94 participants in the vaginal progesterone group and 94 participants in 17-hydroxyprogesterone caproate group were included. Although gestational age at enrollment was similar, those assigned to vaginal progesterone initiated therapy earlier (16.9±1.4 vs 17.8±2.5 weeks; P=.001). Overall continuation of assigned formulation until delivery was similar (73% vs 69%; P=.61). There was no significant difference in preterm birth at37 (31% vs 38%; P=.28; relative risk, 0.81 [95% confidence interval, 0.54-1.20]),34 (9.6% vs 14.9%; P=.26; relative risk, 0.64 [95% confidence interval, 0.29-1.41]), or28 (1.1% vs 4.3%; P=.37; relative risk, 0.25 [95% confidence interval, 0.03-2.20]) weeks of gestation. Participants in the vaginal progesterone group had a later mean gestational age at delivery than participants in the 17-hydroxyprogesterone caproate group (37.36±2.72 vs 36.34±4.10 weeks; mean difference, 1.02 [95% confidence interval, 0.01-2.01]; P=.047).Vaginal progesterone did not reduce the risk of recurrent preterm birth by 50% compared with 17-OHPC; however, vaginal progesterone may lead to increased latency to delivery. This trial was underpowered to detect a smaller, but still clinically significant, difference in the efficacy of preterm birth prevention. Patient factors that impact adherence and ability to obtain medication in a timely fashion should be included in counseling on progesterone selection.

Background Hyperemesis gravidarum (HG) is a common cause of hospital admission in early pregnancy. There is no international consensus on the definition of HG, or on outcomes that should be reported in trials. Consistency in definition and outcome reporting is important for the interpretation and synthesis of data in meta-analyses. Objective To identify which HG definitions and outcomes are currently in use in trials. Search strategy We searched the following sources: (1) Cochrane Central Register of Controlled Trials, (2) Embase and (3) Medline for published trials and the WHO-ICTRP database for ongoing trials (27 October 2017). Selection criteria All randomised clinical trials reporting on any intervention for HG were eligible. Data collection and analysis Two reviewers independently assessed trial eligibility and extracted data on HG definition and outcomes. Main results We included 31 published trials reporting data from 2511 women and three ongoing trials with a planned sample size of 360 participants. We identified 11 definition items. Most commonly used definition items were vomiting (34 trials) and nausea (30 trials). We identified 34 distinct outcomes. Most commonly reported outcomes were vomiting (29 trials), nausea (26 trials), need for hospital treatment (14 trials) and duration of hospital (re)admission(s) (14 trials). Conclusion There is substantial variation of HG definition and outcome reporting in trials. This hampers meaningful aggregation of trial results in meta-analysis and implementation of evidence in guidelines. To overcome this, international consensus on a definition and a core outcome set for HG trials should be developed. Tweetable abstract There is a wide variation of definitions and outcomes reported in trials on hyperemesis gravidarum.

Cervical insufficiency can be defined by a combination of obstetric history, cervical dilation on exam, and/or short cervical length in women with prior preterm birth. Options for mechanical intervention include cerclage and pessary. There is evidence to support the benefit of a cervical cerclage in women with singleton gestations who have a diagnosis of cervical insufficiency either based on second trimester painless cervical dilatation leading to recurrent early preterm births, or a history of early spontaneous preterm birth and a second trimester transvaginal ultrasound short cervical length or cervical dilation on exam. For women with multiple gestations, the benefit of a cerclage is uncertain, and further study is warranted. The pessary has also been studied for mechanical prevention of preterm birth in various populations, however the results so far have been mixed and warrants further study prior to routine use.

To evaluate whether second-trimester cervical length (CL) is associated with induction of labor (IOL) outcomes.Retrospective cohort study of nulliparous singletons undergoing CL screening at 18 0/7-23 6/7 weeks from 1/1/2012 to 12/31/2013. Women induced at term (≥37 weeks) were included. Primary outcome was vaginal delivery (VD) within 24 h. The effect of CL on outcomes was assessed by incidence across CL quartiles and a receiver operating characteristics (ROC) curve. Odds ratios (OR) were adjusted (aOR) for confounders.Two-hundred-and-sixty-eight women were included. Aside from a difference in incidence of prior cervical surgery between CL quartiles (p . 02), other characteristics were similar. Ninety-two women (35%) had a VD within 24 h (versus a CD or VD24 h). A longer a CL was associated with a decreased likelihood of a VD within 24 h with aORs of the third and fourth quartiles of 0.35 (0.16-0.75) and 0.43 (0.21-0.90), respectively, compared to the first quartile. A CL40 mm was predictive of not having a VD within 24 h with a sensitivity of 56%, specificity of 58% and a positive predictive value of 72%.A second-trimester CL40 mm is associated with a decreased likelihood of VD within 24 h in an IOL.

BACKGROUND: Although the use of 17-alpha-hydroxyprogesterone caproate is one of the most commonly used strategies to reduce the risk of preterm birth since its approval by the Food and Drug Administration in 2011, there has been controversy recently that there may be no benefit associated with its use in singleton pregnancies in women with a prior history of spontaneous preterm birth. However, very few of these investigations evaluated the use of intramuscular progesterone in twin pregnancies. A few studies that used 17-alpha-hydroxyprogesterone caproate in twin pregnancies had mainly included unselected twin pregnancies. Although a twin pregnancy is independently associated with an increased likelihood of preterm birth, the primary indication for the use of supplemental progesterone in pregnancy is prior history of spontaneous preterm birth. Therefore, our investigation of weekly intramuscular progesterone in twin pregnancies with this birth history best addresses this question using a selected cohort. OBJECTIVE: To assess whether weekly 17-alpha-hydroxyprogesterone caproate prevents recurrent preterm birth in women with a current twin pregnancy and a prior singleton spontaneous preterm birth. STUDY DESIGN: This was a retrospective cohort study of women with twin pregnancy and a prior singleton spontaneous preterm birth in 2 institutions between January 2005 and December 2016. One group (intervention group) consisted of women who received weekly 17-alpha-hydroxyprogesterone caproate, whereas the other (control group) did not. The primary outcome was twin spontaneous preterm birth

This document addresses the current coronavirus disease 2019 (COVID-19) pandemic for providers and patients in labor and delivery (L&D). The goals are to provide guidance regarding methods to appropriately screen and test pregnant patients for COVID-19 prior to, and at admission to L&D reduce risk of maternal and neonatal COVID-19 disease through minimizing hospital contact and appropriate isolation and provide specific guidance for management of L&D of the COVID-19-positive woman, as well as the critically ill COVID-19-positive woman. The first 5 sections deal with L&D issues in general, for all women, during the COVID-19 pandemic. These include Section 1: Appropriate screening, testing, and preparation of pregnant women for COVID-19 before visit and/or admission to L&D Section 2: Screening of patients coming to L&D triage; Section 3: General changes to routine L&D work flow; Section 4: Intrapartum care; Section 5: Postpartum care; Section 6 deals with special care for the COVID-19-positive or suspected pregnant woman in L&D and Section 7 deals with the COVID-19-positive/suspected woman who is critically ill. These are suggestions, which can be adapted to local needs and capabilities.

Background: Patients with chronic hypertension are at increased risk for superimposed preeclampsia. The 2016 American College of Obstetricians and Gynecologists guideline recommended initiating 81 mg of daily aspirin for all pregnant women with chronic hypertension to prevent superimposed preeclampsia. Objective: (1) To evaluate the rates of implementation of the 2016 American College of Obstetricians and Gynecologists guideline over time; and (2) to evaluate the effectiveness of aspirin for the prevention of superimposed preeclampsia and other adverse maternal and neonatal outcomes in women with chronic hypertension before and after this guideline. Study Design: This is a retrospective study of women with chronic hypertension who delivered at Thomas Jefferson University Hospital from January 2014 through June 2018. This cohort of women with chronic hypertension was divided into 2 groups, before and after the American College of Obstetricians and Gynecologists recommendation published in September 2016. Daily 81 mg of aspirin was initiated between 12 and 16 weeks. We excluded multiple gestations and incomplete records. The primary outcome was incidence of superimposed preeclampsia, and secondary outcomes were incidence of superimposed preeclampsia with or without severe features, small for gestational age, and preterm birth

Objective To use data from the Cervical Length Education and Review program to evaluate the quality of transvaginal cervical length ultrasonography by trained imagers (ie, ultrasonographers, radiologists, perinatologists). Methods This is a retrospective observational study of data from the Cervical Length Education and Review program. Candidates underwent an online lecture series, examination, and submitted a batch of images for review. For a candidate's batch of images to pass, all images must meet at least seven of the nine criteria assessed, the overall batch score needs to be 80% or greater, correct caliper placement must be met for all images, and the same criterion cannot be consistently missed. We also examined a subset of these criteria-appropriate image acquisitions, defined as an image that demonstrated both internal and external os and visualization of the entire endocervical canal. Primary outcome was the overall initial candidate pass rate; secondary outcomes included distribution of criteria missed in images and percentage of images that was inadequately acquired. Results Six hundred eighty-seven candidates submitted 3,748 images between June 10, 2012, and August 18, 2016. Eighty-five percent of candidates were ultrasonographers. Of the 687 initial batches submitted, 105 (15%) did not pass. Eight hundred thirty-seven images (22%) of all images failed at least one criterion; the most common image deficiencies were in "anterior width of cervix equals the posterior width" (33%), "failure to visualize" the internal or external os (29%), "cervix occupies 75% of image and bladder area visible" (33%), and incorrect caliper placement (24%). Two hundred fifty-six (7%) of all images failed to meet our criteria for adequate image acquisition. Conclusion Fifteen percent of trained imagers failed to obtain appropriate cervical length imaging. This highlights the importance of a standardized cervical length training and certification program.